A study of TG4001 and avelumab cancer immunotherapies in advanced HPV-induced malignancies

Phase 1/2

Active, not recruiting

• Conditions: Phase Ib and Phase II part 1: HPV-16 positive recurrent or metastatic malignancies including oropharyngeal squamous cell carcinoma of head and neck, cervical cancer, vulvar cancer, vaginal cancer, penile cancer, anal cancer Phase II part 2: HPV-16 positive recurrent or metastatic malignancies including cervical cancer, vulvar cancer, vaginal cancer, penile cancer, anal cancer

• Registration Number: 2024-515119-23-00
• Lead Sponsor: Transgene

Brief Summary

Phase Ib objective: To evaluate the safety and tolerability of the combination of TG4001 plus avelumab in patients with recurrent or metastatic HPV-16 positive advanced malignancies.

Phase II part 1 objective: To evaluate the efficacy of TG4001 combined to avelumab in terms of Overall Response Rate (ORR) by using RECIST 1.1 in patients with recurrent or metastatic (R/M) HPV-16 positive advanced malignancies including oropharyngeal squamous cell carcinoma of head and neck.

Phase II part 2 objective: To compare the Progression-Free Survival (PFS) of TG4001 in combination with avelumab vs avelumab alone in patients with recurrent or metastatic (R/M) HPV-16 positive advanced malignancies and without liver metastases at baseline.

Detailed Description

Not available

Study Timeline

• Study First Posted: 2024-07-16
• Last Update Posted: 2025-05-14

Recruitment & Eligibility

• Status: Ongoing, recruitment ended
• Sex: Not specified
• Target Recruitment: 142

Inclusion Criteria

Female or male patients, aged at least 18 years (no upper limit of age)

Negative blood pregnancy test at screening for women of childbearing potential

Highly effective contraception for both male and female patients if the risk of conception exists during the study period and for 3 months after the last study treatment administration

ECOG PS 0 or 1

Life expectancy of at least 3 months

Phase Ib and Phase II part 1: Patients with histologically or cytologically documented metastatic or refractory/recurrent HPV-16 + cancer (cervical, vulvar, vaginal, penile, anal cancers and oropharyngeal squamous cell carcinoma of head and neck); Phase II part 2: Patients with HPV-16+ cancers including cervical, vulvar, vaginal, penile, and anal cancer

Disease MUST not be amenable to curative surgery resection or curative radiotherapy with documented disease progression

Prior therapy: Phase Ib and Phase II part 1: Patients MAY have received up to 2 prior lines of systemic chemotherapy for the management of metastatic or recurrent disease; for SCCHN, patients MUST have previously been exposed to platinum-based therapy, either as part of definitive chemoradiation OR as first line systemic treatment for metastatic disease which may include cetuximab. Patients with recurrence/progression within 6 months of prior multimodal therapy using platinum-based therapy are eligible. Patients with cervical cancer may have undergone surgery and/or received definitive radiation or chemo-radiation therapy for localized disease. Phase II part 2: - No more than one prior systemic treatment for recurrent /metastatic disease - Prior treatment for recurrent or metastatic disease is not required for: o Patients with recurrence/progression within 6 months after completion of prior multimodal therapy for localized or locally advanced disease o Patients who are unsuitable for platinum-based therapy o Patients who refuse chemotherapy or other standard therapies for the treatment of metastatic or recurrent disease

For patients with hepatic metastases - no more than 3 hepatic lesions in total (target and non-target lesions) - maximum size of hepatic target disease ≤ 30 mm according to RECIST 1.1

At least one measurable lesion by CT scan according to RECIST 1.1.

Adequate hematological, hepatic and renal function

Exclusion Criteria

Prior exposure to cancer immunotherapy including cancer vaccines, any antibody/drug targeting T cell co-regulatory proteins (immune checkpoints)

Patients with history of interstitial lung disease

Patients with active, known, or suspected auto-immune disease or immunodeficiency, except type I diabetes mellitus, hypothyroidism only requiring hormone replacement or skin disorders (such as vitiligo, psoriasis) not requiring systemic treatment

Significant chronic or acute infections including SARS-CoV-2 (COVID19) PCR positive testing

Clinically significant (that is, active) cardiovascular disease: cerebral vascular accident/stroke or myocardial infarction (< 6 months prior to enrollment), unstable angina pectoris, congestive heart failure (New York Heart Association Classification Class ≥ II), or serious uncontrolled cardiac arrhythmia requiring medication/active intervention

History of uncontrolled intercurrent illness including but not limited to: - Hypertension uncontrolled by standard therapies (not stabilized to 150/90 mmHg or lower) - Uncontrolled diabetes (e.g., hemoglobin A1c ≥ 8%)

Patients under chronic treatment with systemic corticosteroids or other immunosuppressive drugs for a period of at least 4 weeks and whose treatment was not stopped 2 weeks prior to the first study treatment, with the exception of patients with adrenal insufficiency who may continue corticosteroids at physiological replacement dose, equivalent to ≤ 10 mg prednisone daily. Steroids with no or minimal systemic effect (topical, inhalation) are allowed

Patients with CNS metastases except those with brain metastases treated locally and clinically stable during 4 weeks prior to start of study treatment, and those without ongoing neurological symptoms that are related to the brain localization of the disease

Other active malignancy requiring concurrent systemic intervention

Patients with previous malignancies other than the target malignancy to be investigated in this trial (except non-melanoma skin cancers, and the following in situ cancers: bladder, gastric, colon, endometrial, cervical/dysplasia, melanoma, or breast) are excluded unless a complete remission was achieved at least 2 years prior to study entry AND no additional therapy is required during the study period

Patient with any organ transplantation, including allogeneic stem cell transplantation

Known severe hypersensitivity reactions to monoclonal antibodies (Grade ≥ 3 NCI-CTC V4.03), any history of anaphylaxis, or uncontrolled asthma

Any known allergy or reaction to eggs, gentamycin or attributed to compounds of similar chemical or biological composition to therapeutic vaccines/immunotherapeutic products

Any known allergy or reaction to any component of anti-PD-L1/PD-1 or its excipients

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Phase II part 1: overall response rate according to RECIST 1.1		Phase II part 1: overall response rate according to RECIST 1.1
Phase Ib: safety and tolerability		Phase Ib: safety and tolerability
Phase II part 2: progression-free survival according to RECIST 1.1		Phase II part 2: progression-free survival according to RECIST 1.1

Secondary Outcome Measures

Name	Time	Method
Phase Ib and phase II part 2: Overall response rate by using RECIST 1.1		Phase Ib and phase II part 2: Overall response rate by using RECIST 1.1
Phase Ib and phase II part 1: Progression Free Survival (PFS)		Phase Ib and phase II part 1: Progression Free Survival (PFS)
Overall Survival (OS)		Overall Survival (OS)
Duration of Response (DoR)		Duration of Response (DoR)
Overall safety profile		Overall safety profile
Phase Ib: Overall response rate by using RECIST 1.1 and overall safety profile		Phase Ib: Overall response rate by using RECIST 1.1 and overall safety profile
Percentage of patients with liver metastases at baseline who have disease progression at D43 (phase II part 2)		Percentage of patients with liver metastases at baseline who have disease progression at D43 (phase II part 2)

Trial Locations

Locations (17)

Hospital Germans Trias I Pujol; 🇪🇸 Badalona, Spain

Hospital General Universitario De Valencia; 🇪🇸 Valencia, Spain

Hospital Universitario Virgen De La Victoria; 🇪🇸 Malaga, Spain

Hospital Clinico San Carlos; 🇪🇸 Madrid, Spain

Hospital Universitario 12 De Octubre; 🇪🇸 Madrid, Spain

Hospital Universitario Virgen De Las Nieves; 🇪🇸 Granada, Spain

Oncopole Claudius Regaud; 🇫🇷 Toulouse Cedex 9, France

Centre Hospitalier De Colmar; 🇫🇷 Colmar Cedex, France

Institut Curie; 🇫🇷 Paris, France

Institut Gustave Roussy; 🇫🇷 Villejuif, France

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Hospital Germans Trias I Pujol

🇪🇸Badalona, Spain

Iris Teruel

Site contact

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iteruel@iconcologia.net